Bacterial meningitis is a significant cause of mortality and morbidity, especially in infants and young children. Although 85-95 % of persons contracting meningitis currently survive, significant neurological sequelae occur in approximately one third of these long-term survivors. The objective of the proposed research is to investigate the pathogenesis and prevention of Haemophilus influenzae meningitis. These studies will utilize an animal model. Our previous and continuing investigations have shown that intranasal inoculation of infant rats with Haemophilus influenzae type b results in bacteremia and meningitis. The histologic characteristics of the meningitis, the CSF findings and the age-related susceptibility of infant rats to sepsis and meningitis resemble the disease as it occurs in infants and children. Using this infant rat model, we aim to: 1. Study the invasion of the meninges by hematogenous dissemination of Haemophilus influenzae b in order to demonstrate where the bacteria enter the CNS. 2. Study the role of the spleen as a determinant of meningeal invasion by H. influenzae b. 3. Study the potential of cross-reacting bacteria to prime for protective immunity to invasive H. influenzae b infection.